Herpes simplex virus (“HSV”) infections are extremely prevalent and have a range of manifestations from apparently asymptomatic acquisition to severe disease and life threatening infections in the immunocompromised individual and the neonate. These infections are caused by two viruses, herpes simplex virus type 1 (“HSV-1”) and herpes simplex virus type 2 (“HSV-2”). HSV-1 is the predominant cause of oral infections and is usually acquired in childhood, whereas HSV-2 infections are usually sexually transmitted genital infections. These distinctions are blurred, however, and up to 25% of genital herpes is caused by HSV-1. Following initial infection, the virus establishes a life long latent state and periodically reactivates, causing clinically apparent lesional episodes or asymptomatic virus shedding.
In general, HSV is a double-stranded DNA virus having a genome of about 150-160 kbp packaged within an icosahedral nucleocapsid enveloped in a membrane. The membrane (or envelope) includes 10 or more virus-specific glycolproteins, the most abundant of which are gB, gC, gD, and gE. The viral genome also encodes over 50 other proteins including the tegument protein VP16. The viral genomes of HSV-1 and HSV-2 are colinear and share 50% homology over the entire genome. For some genes, such as gB and gD, the amino acid identity between the two virus types increases up to as much as 80 to 90%. As a result of this similarity, many HSV-specific antibodies are cross-reactive for both virus types. Within a virus type, there is a limited (1 to 2%) strain-to-strain sequence variability of the glycoprotein genes.
The prevalence of asymptomatic HSV-2 infections has been difficult to determine because of the strong cross-neutralization between HSV-1 and HSV-2 and because of the high incidence of antibody to HSV-1 in the population. Specificity of such an assay is important because of the implications of HSV-2 infections both at the epidemiological level, for example, the relation of genital herpes to cervical cancer, and at the individual level, for example, false-positive results can lead to great problems such as improper medical management for pregnant women or undue psychological trauma in patients and their consorts.
There remains a need in the field for methods for detecting HSV-2 in a manner that is rapid, sensitive and specific, particularly with respect to the ability to differentiate accurately and definitively between HSV-1 and HSV-2.
The present invention addresses these needs.